dengue and its association with atypical lymphocytes

1. UTILITY OF ATYPICAL LYMPHOCYTES AND
LARGE IMMATURE CELLS IN PREDICTION
OF DENGUE SEVERITY SLIDESHARE
CHAIRPERSON: Dr. K. V. Srinivas PROFESSOR
DEPT OF GENERAL MEDICINE
DR B R AMBEDKAR MEDICAL COLLEGE
PRESENTER: Dr. Raghavendra C M PG RESIDENT (JR1)
DEPT OF GENERAL MEDICINE
DR B R AMBEDKAR MEDICAL COLLEGE.

2. • PUBLISHED in 08/07/2023
• AUTHORS AFFILATIONS: RAMADEVI PERAKA (ASSOCIATE PROFESSOR,
DEPARTMENT OF PATHOLOGY, APOLLO INSTITUTE OF MEDICAL
SCIENCES & RESEARCH, APOLLO HEALTH CITY CAMPUS), ADITYA
KOPPULA (RESEARCH SCHOLAR, DEPARTMENT OF BIOMEDICAL
ENGINEERING, INDIAN INSTITUTE OF TECHNOLOGY), BABY SHALINI
MUPPALA (ASSOCIATE PROFESSOR, DEPARTMENT OF INTERNAL
MEDICINE), MANI M PARSA (PROFESSOR, DEPARTMENT OF
PATHOLOGY, APOLLO INSTITUTE OF MEDICAL SCIENCES & RESEARCH,
APOLLO HEALTH CITY CAMPUS, HYDERABAD, TELANGANA, INDIA)
• STUDY TYPE: SINGLE CENTRE RETROSPECTIVE STUDY
• STUDY DURATION: OCTOBER 2019 TO 2022

3. • INTRODUCTION
• NEED FOR THE STUDY
• METHODOLOGY
• RESULTS
• DISCUSSION
• LIMITATIONS
• STRENGTHS OF THE STUDY
• CONCLUSION
• CRITICAL ANALYSIS
• APPLICABILITY IN OUR SETUP

4. INTRODUCTION
• Dengue is a mosquito -borne viral hemorrhagic fever caused by the
Dengue virus, a flavivirus. It is transmitted by the bite of infected
Aedes mosquitoes.
• 390 million dengue virus infections globally every year, of which 96
million show clinical manifestations and approximately 40,000
succumb to the disease annually.
• In India, 7,95,211 cases were reported, with 1,151 fatalities for 2017–
2022.

5. • Four predominant serotypes (DEN-1, 2, 3, 4) The virus is endowed
with three structural proteins (capsid C, membrane M, and envelope
E) and seven nonstructural (NS) proteins.
• Primary infection induces lifelong immunity specific to the causal
serotype.
• Second infection by a different serotype is thought to increase the risk
for severe dengue.

6. • Virus thrives inside the cell, creating an inflammatory cascade that
culminates in the cardinal features of severe dengue, viz, vascular
leakage, fluid accumulation, thrombocytopenia, shock, MODS, DIC
and potential death.
• Cross-reactive T cells, NS1 antigen, anti-dengue virus NS1 antibodies,
and autoimmunity contribute to the pathophysiology of dengue
complications.

7. • Natural history of dengue fever has three stages/phases (1) the acute
febrile phase (2) the critical phase following the defervescence (3) the
recovery phase
• Severe dengue with all attendant complications generally occurs after
the febrile phase in the critical stage when the hematocrit rises and
the platelets fall

8. • DENGUE- WITH or WITHOUT WARNING SIGNS
• PROBABLE DENGUE- Clinical features
• Nausea, vomiting (New)
• Rash
• Aches and pains
• Tourniquet test positive
• Leukopenia
• Any warning sign (New)
• WARNING SIGNS:
• Abdominal pain or tenderness
• Persistent vomiting
• Clinical fluid accumulation
• Mucosal bleed
• Lethargy or restlessness
• Liver enlargement > 2 cm
• Laboratory finding of increasing HCT concurrent with rapid decrease in
platelet count

9. NEED FOR THE STUDY
• Determine time trends in hematological parameters indicative of
pathophysiological features of severe dengue, viz, plasma leakage
(rising hematocrit) and thrombocytopenia.
• Determine the association of the longitudinal patterns in atypical
lymphocyte and large immature cell with time trends in platelet
counts and hematocrit.

10. METHODOLOGY
• STUDY DESIGN: Retrospective data analysis was done on (n = 79)
consecutive dengue patients hospitalized between October 2019 to
2022.
• STUDY POPULATION: NS1 antigen and immunoglobulin M antibody
POSITIVE PATIENTS (Enzyme-linked immunosorbent assay confirmed).
• Inclusion criteria: NS1 antigen and immunoglobulin M antibody POSITIVE
PATIENTS (Enzyme-linked immunosorbent assay confirmed)
• Exclusion criteria: ELISA NEGATIVE NS1 antigen and immunoglobulin M
antibody POSITIVE PATIENTS

12. RESULT
• Every 1% increase in atypical lymphocyte percentage is associated
with a decrease in platelet count by 16,963 cells/mm3 . This suggests
that the ATY may play a causal role in the platelet count fluctuations
in dengue.
• A similar albeit weaker relation was found between platelet count
and LIC, with a platelet count fall by 6,680 cells/mm3 for every 1%
rise in LICs.

18. DISCUSSION
• To Explore the predictors of platelet counts, focusing on the ATY and
large immature cell fraction data from 79 patients.
• Atypical lymphocytes fluctuated in lock-step with the platelet count
but in an anticorrelated manner with lower platelet counts whenever
the atypical lymphocytes increased and vice versa.
• Suggest atypical lymphocytes play a potentially causal role in the
decline of platelet counts in dengue.

19. • Jampangern et al. 2007 study suggested that significant positive
correlation between atypical lymphocytes and a cluster of
differentiation 19 (CD19) + B cells.
• LIC TC et al study suggested that presence of T cell markers (CD2 and
CD7) on atypical lymphocytes
• This study conjecture that atypical lymphocytosis reflects the
heightened and misdirected adaptive immune response to dengue
characterized by the triad of crossreacting B and T cells, cytokine
storm, and autoimmunity leading to tissue damage causing dengue
pathophysiology.

20. CONCLUSION
• Association between atypical lymphocytes and the pathognomonic
hematological changes of dengue, viz, platelet count and hematocrit.
• This study also supports the predictive potential of ATY and LIC in
dengue.

21. LIMITATIONS
• There is a paucity of effective prognostic markers for the cardinal
pathophysiological feature of dengue, viz, vascular leakage and its
severity.